Q8K4D7 (PLCZ1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1
EC=3.1.4.11

Alternative name(s):
Phosphoinositide phospholipase C-zeta-1
Phospholipase C-zeta-1
Short name=PLC-zeta-1

Gene names

Name:

Plcz1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	647 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. In vitro, hydrolyzes PtdIns(4,5)P2 in a Ca2+-dependent manner. Triggers intracellular Ca2+ oscillations in oocytes solely during M phase and is involved in inducing oocyte activation and initiating embryonic development up to the blastocyst stage. Is therefore a strong candidate for the egg-activating soluble sperm factor that is transferred from the sperm into the egg cytoplasm following gamete membrane fusion. May exert an inhibitory effect on phospholipase-C-coupled processes that depend on calcium ions and protein kinase C, including CFTR trafficking and function. Ref.1 Ref.2 Ref.5 Ref.6 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 UniProtKB Q86YW0
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. UniProtKB P10688
Cofactor	Calcium. Ref.8
Subunit structure	Interacts via its C2 domain with PtdIns3P and, to a lesser extent, PtdIns5P in vitro. Ref.8
Subcellular location	Nucleus. Cytoplasm › perinuclear region. Note: Exhibits alternative cytoplasmic/nuclear localization during development. Translocates from the pronucleus into cytoplasm upon nuclear envelope breakdown for mitosis and localizes again to the pronuclei at interphase following meiosis and mitosis. Ref.2 Ref.5 Ref.6 Ref.7 Ref.13
Tissue specificity	Highly expressed in postpuberal testis, where expression is sperm cell-specific. Also expressed in brain of both sexes. Ref.1
Domain	The EF-hand and C2 domains are essential for triggering Ca2+ oscillating activity and the regulation of PLCZ1 enzyme activity. Ref.8 Ref.9 Ref.10 Ref.12 The X-Y linker region between PI-PLC X-box and Y-box domains may be a target for proteolysis and may play an important regulatory role during fertilization. Ref.8 Ref.9 Ref.10 Ref.12
Miscellaneous	Transgenic mice, where broad ectopic expression is forced, initially appear healthy and their oocytes undergo unperturbed meiotic maturation to metaphase II but subsequently exhibit autonomous intracellular free calcium oscillations, second polar body extrusion, pronucleus formation and parthenogenetic development. Transgenic males remained largely asymptomatic, whereas transgenic females develop abdominal swellings caused by benign ovarian teratomas.
Sequence similarities	Contains 1 C2 domain. Contains 1 EF-hand domain. Contains 1 PI-PLC X-box domain. Contains 1 PI-PLC Y-box domain.

Ontologies

Keywords
Biological process	Fertilization Lipid degradation Lipid metabolism
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Calcium
Molecular function	Developmental protein Hydrolase Transducer
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion transport Inferred from direct assay Ref.1. Source: MGI egg activation Inferred from direct assay Ref.1. Source: MGI intracellular signal transduction Inferred from electronic annotation. Source: InterPro lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro phosphatidylinositol phospholipase C activity Inferred from electronic annotation. Source: EC phospholipase C activity Inferred from direct assay Ref.1. Source: MGI signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 Ref.2 Ref.3 Ref.4 (identifier: Q8K4D7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 Ref.2 (identifier: Q8K4D7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-110: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 647	647	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1		PRO_0000347246
Regions
	Domain	43 – 78	36	EF-hand
	Domain	163 – 307	145	PI-PLC X-box
	Domain	386 – 502	117	PI-PLC Y-box
	Domain	507 – 610	104	C2
Sites
	Active site	178	1	By similarity UniProtKB P10688
	Active site	223	1	By similarity UniProtKB P10688
Natural variations
	Alternative sequence	1 – 110	110	Missing in isoform 2. Ref.2		VSP_052863
Experimental info
	Mutagenesis	210	1	D → R: Defective in Ca(2+) oscillation activity and shows slower nuclear translocation. Ref.10
	Mutagenesis	299	1	K → E: Defective in Ca(2+) oscillation activity and loss of nuclear translocation. Ref.10
	Mutagenesis	301	1	K → E: Defective in Ca(2+) oscillation activity and loss of nuclear translocation. Ref.10
	Mutagenesis	376	1	R → E: Abolishes nuclear translocation. Ref.10
	Mutagenesis	377	1	K → E: Abolishes nuclear translocation. Prolongs Ca(2+) oscillations allowing them to occur during interphase. Ref.6 Ref.10
	Mutagenesis	378	1	R → E: Abolishes nuclear translocation. Ref.10
	Mutagenesis	379	1	K → E: Abolishes nuclear translocation. Ref.10
	Mutagenesis	381	1	K → E: Abolishes nuclear translocation. Ref.10
	Sequence conflict	58	1	Q → H in AAI06768. Ref.4
	Sequence conflict	360	1	R → K in AAI06768. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: ABE24E5CCCC63CA2	FASTA	647	74,614
	10 20 30 40 50 60 MESQLHELAE ARWFLSKVQD DFRGGKINVE ITHKLLEKLD FPCHFAHVKH IFKENDRQNQ 70 80 90 100 110 120 GRITIEEFRA IYRCIVHREE ITEIFNTYTE NRKILSENSL IEFLTQEQYE MEIDHSDSVE 130 140 150 160 170 180 IINKYEPIEE VKGERQMSIE GFARYMFSSE CLLFKENCKT VYQDMNHPLS DYFISSSHNT 190 200 210 220 230 240 YLISDQILGP SDIWGYVSAL VKGCRCLEID CWDGSQNEPI VYHGYTFTSK LLFKTVVQAI 250 260 270 280 290 300 NKYAFVTSDY PVVLSLENHC SPGQQEVMAS ILQSTFGDFL LSDMLEEFPD TLPSPEALKF 310 320 330 340 350 360 KILVKNRKVG TLSETHERIG TDKSGQVLEW KEVIYEDGDE DSGMDPETWD VFLSRIKEER 370 380 390 400 410 420 EADPSTLSGI AGVKKRKRKM KIAMALSDLV IYTKAEKFRN FQYSRVYQQF NETNSIGESR 430 440 450 460 470 480 ARKLSKLRVH EFIFHTAAFI TRVYPKMMRA DSSNFNPQEF WNVGCQMVAL NFQTPGLPMD 490 500 510 520 530 540 LQNGKFLDNG GSGYILKPDI LRDTTLGFNP NEPEYDDHPV TLTIRIISGI QLPVSSSSNT 550 560 570 580 590 600 PDIVVIIEVY GVPNDHVKQQ TRVVKNNAFS PKWNETFTFL IQVPELALIR FVVETQQGLL 610 620 630 640 SGNELLGQYT LPVLCMNKGY RRVPLFSKSG ANLEPSSLFI YVWYFRE
	Isoform 2 [UniParc]. Checksum: 4B6832D35A65F75F	FASTA	537	61,307
	10 20 30 40 50 60 MEIDHSDSVE IINKYEPIEE VKGERQMSIE GFARYMFSSE CLLFKENCKT VYQDMNHPLS 70 80 90 100 110 120 DYFISSSHNT YLISDQILGP SDIWGYVSAL VKGCRCLEID CWDGSQNEPI VYHGYTFTSK 130 140 150 160 170 180 LLFKTVVQAI NKYAFVTSDY PVVLSLENHC SPGQQEVMAS ILQSTFGDFL LSDMLEEFPD 190 200 210 220 230 240 TLPSPEALKF KILVKNRKVG TLSETHERIG TDKSGQVLEW KEVIYEDGDE DSGMDPETWD 250 260 270 280 290 300 VFLSRIKEER EADPSTLSGI AGVKKRKRKM KIAMALSDLV IYTKAEKFRN FQYSRVYQQF 310 320 330 340 350 360 NETNSIGESR ARKLSKLRVH EFIFHTAAFI TRVYPKMMRA DSSNFNPQEF WNVGCQMVAL 370 380 390 400 410 420 NFQTPGLPMD LQNGKFLDNG GSGYILKPDI LRDTTLGFNP NEPEYDDHPV TLTIRIISGI 430 440 450 460 470 480 QLPVSSSSNT PDIVVIIEVY GVPNDHVKQQ TRVVKNNAFS PKWNETFTFL IQVPELALIR 490 500 510 520 530 FVVETQQGLL SGNELLGQYT LPVLCMNKGY RRVPLFSKSG ANLEPSSLFI YVWYFRE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development." Saunders C.M., Larman M.G., Parrington J., Cox L.J., Royse J., Blayney L.M., Swann K., Lai F.A. Development 129:3533-3544(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Strain: C57BL/6J. Tissue: Spermatid.
[2]	"Recombinant phospholipase Czeta has high Ca2+ sensitivity and induces Ca2+ oscillations in mouse eggs." Kouchi Z., Fukami K., Shikano T., Oda S., Nakamura Y., Takenawa T., Miyazaki S. J. Biol. Chem. 279:10408-10412(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION. Tissue: Testis.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Mammalian phospholipase Czeta induces oocyte activation from the sperm perinuclear matrix." Fujimoto S., Yoshida N., Fukui T., Amanai M., Isobe T., Itagaki C., Izumi T., Perry A.C.F. Dev. Biol. 274:370-383(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Cell cycle-dependent Ca2+ oscillations in mouse embryos are regulated by nuclear targeting of PLCzeta." Larman M.G., Saunders C.M., Carroll J., Lai F.A., Swann K. J. Cell Sci. 117:2513-2521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-377.
[7]	"Nuclear translocation of phospholipase C-zeta, an egg-activating factor, during early embryonic development." Sone Y., Ito M., Shirakawa H., Shikano T., Takeuchi H., Kinoshita K., Miyazaki S. Biochem. Biophys. Res. Commun. 330:690-694(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"The role of EF-hand domains and C2 domain in regulation of enzymatic activity of phospholipase Czeta." Kouchi Z., Shikano T., Nakamura Y., Shirakawa H., Fukami K., Miyazaki S. J. Biol. Chem. 280:21015-21021(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COFACTOR, INTERACTION WITH PTDINS(3)P AND PTDINS(5)P, DOMAIN.
[9]	"Role of phospholipase C-zeta domains in Ca2+-dependent phosphatidylinositol 4,5-bisphosphate hydrolysis and cytoplasmic Ca2+ oscillations." Nomikos M., Blayney L.M., Larman M.G., Campbell K., Rossbach A., Saunders C.M., Swann K., Lai F.A. J. Biol. Chem. 280:31011-31018(2005) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN.
[10]	"The role of X/Y linker region and N-terminal EF-hand domain in nuclear translocation and Ca2+ oscillation-inducing activities of phospholipase Czeta, a mammalian egg-activating factor." Kuroda K., Ito M., Shikano T., Awaji T., Yoda A., Takeuchi H., Kinoshita K., Miyazaki S. J. Biol. Chem. 281:27794-27805(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DOMAIN, MUTAGENESIS OF ASP-210; LYS-299; LYS-301; ARG-376; LYS-377; ARG-378; LYS-379 AND LYS-381.
[11]	"Broad, ectopic expression of the sperm protein PLCZ1 induces parthenogenesis and ovarian tumours in mice." Yoshida N., Amanai M., Fukui T., Kajikawa E., Brahmajosyula M., Iwahori A., Nakano Y., Shoji S., Diebold J., Hessel H., Huss R., Perry A.C. Development 134:3941-3952(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, OVEREXPRESSION.
[12]	"Proteolytic processing of phospholipase Czeta and [Ca2+]i oscillations during mammalian fertilization." Kurokawa M., Yoon S.Y., Alfandari D., Fukami K., Sato K., Fissore R.A. Dev. Biol. 312:407-418(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DOMAIN.
[13]	"Difference in Ca2+ oscillation-inducing activity and nuclear translocation ability of PLCZ1, an egg-activating sperm factor candidate, between mouse, rat, human, and medaka fish." Ito M., Shikano T., Oda S., Horiguchi T., Tanimoto S., Awaji T., Mitani H., Miyazaki S. Biol. Reprod. 78:1081-1090(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF435950 mRNA. Translation: AAM95914.1. AK006672 mRNA. No translation available. BC106767 mRNA. Translation: AAI06768.1.
IPI	IPI00172259. IPI00903377.
RefSeq	NP_473407.2. NM_054066.4.
UniGene	Mm.50808.
3D structure databases
ProteinModelPortal	Q8K4D7.
SMR	Q8K4D7. Positions 26-642.
ModBase	Search...
PTM databases
PhosphoSite	Q8K4D7.
Proteomic databases
PRIDE	Q8K4D7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000032356; ENSMUSP00000032356; ENSMUSG00000030230.
GeneID	114875.
KEGG	mmu:114875.
UCSC	uc009eny.1. mouse.
Organism-specific databases
CTD	89869.
MGI	MGI:2150308. Plcz1.
Phylogenomic databases
eggNOG	NOG149692.
GeneTree	ENSGT00700000104181.
HOGENOM	HOG000006871.
HOVERGEN	HBG053610.
InParanoid	Q8K4D7.
KO	K05861.
OMA	CIVHREE.
OrthoDB	EOG4X0MSB.
Enzyme and pathway databases
BRENDA	3.1.4.11. 3474.
Gene expression databases
ArrayExpress	Q8K4D7.
Bgee	Q8K4D7.
Genevestigator	Q8K4D7.
Family and domain databases
Gene3D	1.10.238.10. 2 hits. 3.20.20.190. 2 hits.
InterPro	IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR018029. C2_membr_targeting. IPR011992. EF-hand-like_dom. IPR002048. EF_hand_dom. IPR001192. Pinositol_PLipase_C. IPR017946. PLC-like_Pdiesterase_TIM-brl. IPR015359. PLipase_C_EF-hand-like. IPR000909. PLipase_C_PInositol-sp_X_dom. IPR001711. PLipase_C_Pinositol-sp_Y. [Graphical view]
PANTHER	PTHR10336. PTHR10336. 1 hit.
Pfam	PF00168. C2. 1 hit. PF09279. efhand_like. 1 hit. PF00388. PI-PLC-X. 1 hit. PF00387. PI-PLC-Y. 1 hit. [Graphical view]
PRINTS	PR00390. PHPHLIPASEC.
SMART	SM00239. C2. 1 hit. SM00148. PLCXc. 1 hit. SM00149. PLCYc. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF51695. PLC-like_Pdiesterase_TIM-brl. 1 hit.
PROSITE	PS50004. C2. 1 hit. PS00018. EF_HAND_1. False negative. PS50222. EF_HAND_2. 1 hit. PS50007. PIPLC_X_DOMAIN. 1 hit. PS50008. PIPLC_Y_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	368899.
SOURCE	Search...

Entry information

Entry name

PLCZ1_MOUSE

Accession

Primary (citable) accession number: Q8K4D7
Secondary accession number(s): Q3KPE5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 2, 2008
Last sequence update:	October 1, 2002
Last modified:	May 29, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program